The invention relates to controlled long-acting release pharmaceutical formulations containing an active therapeutic agent and a carrier base material. More specifically, this invention relates to tablets of a controlled long-acting pharmaceutical formulation containing an active therapeutic agent and a carrier base material.
Long-acting products are widely marketed in the pharmaceutical field and are now a significant factor in the administration of a variety of active pharmaceutical agents. The advantages of such long-acting or sustained release products are well understood and a very substantial industry has developed around these products. Sustained release products permit various medications to be administered for uniform and continuous release over a prolonged period of time, thereby achieving a particular blood level of active ingredient for whatever time is thought to be advantageous to the patient. Such administration obviates the necessity of frequent administration of active ingredient and avoids the problems inherent in insuring timely and repetitive consumption of pharmaceutical product by the patient. It is possible to achieve stable blood levels of a variety of active therapeutic agents and thereby control a variety of physiological conditions. It also reduces or possibly eliminates toxic or side effects which are caused by frequent administration of active ingredients through the peaks and valleys of blood levels caused by multiple ingestion of medication.
In the production of controlled or sustained release tablets by direct compression of dry powders, a water soluble thickener is commonly used to provide a matrix for the tablet. The thickener hydrates rapidly on the surface of the tablet and swells to a gelatinous consistency through which the drug must diffuse, thus decreasing the rate of diffusion of the active drug.
Alginates derived from natural sources such as kelp, i.e. "algal alginates", are used in controlled release tablets. One of the disadvantages in using algal alginates to control release is that they are highly dependent on the pH condition of the dissolution medium. In gastric fluids, at low pH, they produce a gelled layer on the surface of the tablet which retards diffusion of the active ingredient. As pH conditions increase, however (e.g. in the intestine), algal alginates rapidly dissolve, becoming less capable of influencing drug diffusion.
The following patents describe various controlled release systems which include algal alginates.
Wheatley et al., U.S. Pat. No. 4,933,185, describes a system for controlled release of biologically active substances such as proteins. The system contains the active substance and a polysaccharide degrading enzyme encapsulated within a microcapsule. The microcapsule has an inner polysaccharide polymer core and an outer ionically interacting skin. One of the exemplary polysaccharides is alginate.
Hotder et al., U.S. Pat. No. 4,842,866, describes a controlled release system which contains an active ingredient, sodium alginate, and a calcium-sodium alginate complex. The amount of calcium used in the calcium-sodium alginate complex is precisely controlled, and the complex is self-gelling.
Connick, U.S. Pat. No. 4,401,456, describes a process for producing alginate gel beads containing an herbicide material.
Gyarmati et al., U.S. Pat. No. 4,199,560, describe solid oral pharmaceutical products with protracted active ingredient release. Tablet internal phase is composed of a hydrophobic component and a hydrophilic component.
Mitra, U.S. Pat. No. 4,163,777, describes controlled antacid delivery using polysaccharide, including sodium alginate.
Scher, U.S. Pat. No. 4,053,627, describes a method for controlling the release of an insect juvenile, hormone from chemical degradation by incorporating the hormone into gel discs containing water soluble sodium alginate, a calcium salt for gelatinization, a solubilizing agent, and a biocide.
The present invention is a controlled or sustained release tablet comprising an active ingredient and a microbially produced alginate-type polysaccharide ("bioalgin"), which is effective for controlling release of the active ingredient in the stomach or the intestine.